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EEPD1 promotes repair of oxidatively-stressed replication forks

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Title
EEPD1 promotes repair of oxidatively-stressed replication forks
Author(s)
Jaiswal, Aruna S.; Hyun-Suk Kim; Orlando D. Schärer; Sharma, Neelam; Williamson, Elizabeth A.; Srinivasan, Gayathri; Phillips, Linda; Kong, Kimi; Arya, Shailee; Misra, Anurag; Dutta, Arijit; Gupta, Yogesh; Walter, Christi A.; Burma, Sandeep; Narayan, Satya; Sung, Patrick; Nickoloff, Jac A.; Hromas, Robert
Publication Date
2023-03
Journal
NAR Cancer, v.5, no.1
Publisher
Oxford University Press
Abstract
Unrepaired oxidatively-stressed replication forks can lead to chromosomal instability and neoplastic transformation or cell death. To meet these challenges cells have evolved a robust mechanism to repair oxidative genomic DNA damage through the base excision repair (BER) pathway, but less is known about repair of oxidative damage at replication forks. We found that depletion or genetic deletion of EEPD1 decreases clonogenic cell survival after oxidative DNA damage. We demonstrate that EEPD1 is recruited to replication forks stressed by oxidative damage induced by H2O2 and that EEPD1 promotes replication fork repair and restart and decreases chromosomal abnormalities after such damage. EEPD1 binds to abasic DNA structures and promotes resolution of genomic abasic sites after oxidative stress. We further observed that restoration of expression of EEPD1 via expression vector transfection restores cell survival and suppresses chromosomal abnormalities induced by oxidative stress in EEPD1-depleted cells. Consistent with this, we found that EEPD1 preserves replication fork integrity by preventing oxidatively-stressed unrepaired fork fusion, thereby decreasing chromosome instability and mitotic abnormalities. Our results indicate a novel role for EEPD1 in replication fork preservation and maintenance of chromosomal stability during oxidative stress. © 2023 The Author(s).
URI
https://pr.ibs.re.kr/handle/8788114/13641
DOI
10.1093/narcan/zcac044
ISSN
2632-8674
Appears in Collections:
Center for Genomic Integrity(유전체 항상성 연구단) > 1. Journal Papers (저널논문)
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